Novel dihydrochalcone from Fissistigma latifolium targets STAT3 and survivin to overcome multidrug resistance cancers in vitro and in vivo
Year: 2025
Type: article
Abstract: BACKGROUND: Multidrug resistance (MDR) remains a significant challenge in cancer chemotherapy, with no FDA-approved drugs currently available for its treatment. Natural chalcones, known for their diverse bioactivities, have emerged as potential therapeutic candidates. PURPOSE: This study aimed to investigate the potential of 4,6-dimethoxy-2,5-quinodihydrochalcone (DODHC), a compound derived from Fissistigma latifolium, in overcoming MDR in cancer and to elucidate its underlying molecular mechanisms. METHODS: The reversal effects of DODHC on MDR were evaluated using cytotoxicity assays. The molecular mechanisms were explored through apoptosis- and cell cycle-related assays, STAT3 ELISA, western blotting, docking simulations, and a zebrafish model. The impact of DODHC on P-glycoprotein (P-gp) activity was assessed using the Calcein-AM uptake assay. RESULTS: DODHC promoted apoptosis in MDR cancer cells by suppressing survivin expression and activating the extrinsic apoptotic pathway. It also induced G2/M phase cell cycle arrest by downregulating cell division control protein 2 (CDC2) and cyclin B1 (CCNB1), thereby inhibiting cell proliferation. Additionally, DODHC reduced both total and phosphorylated STAT3 levels in MDR cancer cells without affecting P-gp activity. In vivo, DODHC significantly inhibited tumor growth in MDR cancer models, both as a monotherapy and in combination with paclitaxel. CONCLUSION: This study highlights DODHC as a dual inhibitor of STAT3 and survivin, demonstrating its potential as a promising candidate for the treatment of MDR cancers.
Source: Biomedicine & Pharmacotherapy
Authors: I-Ting Wu, Ying-Tzu Chang, Ching-Hui Su, Yu-Hsuan Lan, Chin-Chuan Hung
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,610
OpenAlex ID: W4410080299